Post-translational modifications regulate the ticking of the circadian clock

@article{Gallego2007PosttranslationalMR,
  title={Post-translational modifications regulate the ticking of the circadian clock},
  author={Monica Gallego and David M. Virshup},
  journal={Nature Reviews Molecular Cell Biology},
  year={2007},
  volume={8},
  pages={139-148}
}
Getting a good night's sleep is on everyone's to-do list. So is, no doubt, staying awake during late afternoon seminars. Our internal clocks control these and many more workings of the body, and disruptions of the circadian clocks predispose individuals to depression, obesity and cancer. Mutations in kinases and phosphatases in hamsters, flies, fungi and humans highlight how our timepieces are regulated and provide clues as to how we might be able to manipulate them. 

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References

SHOWING 1-10 OF 116 REFERENCES

A Rhythmic Ror

Circadian Clock Control by SUMOylation of BMAL1

BMAL1, an essential transcription factor component of the clock mechanism, is SUMOylated on a highly conserved lysine residue (Lys259) in vivo, revealing an additional level of regulation within the core mechanism of the circadian clock.

Molecular genetics of timing in intrinsic circadian rhythm sleep disorders

This work reports the discovery of a point mutation in a human clock gene that produces a sleep phase syndrome, and suggests that other intrinsic sleep disorders may have genetic underpinnings, and that less debilitating variations in sleep/wake behavior may be revealed by molecular screening of known clock genes in broader human populations.

A role for the proteasome in the light response of the timeless clock protein.

The sensitivity of TIM regulation by light was tested and suggested that TIM is degraded through a ubiquitin-proteasome mechanism, and TIM was ubiquitinated in response to light in cultured cells.
...